The impact of diabetes on the relationship of coronary artery disease and outcome: a study using multimodality imaging

Among 1743 patients, 1214 had no diabetes (69.7%), 259 had prediabetes (14.9%), and 270 had type 2 diabetes (15.5%). Patient characteristics are shown in Table 1.

Table 1 Clinical characteristics, medication, imaging findings, early invasive procedures, and outcomes during follow-up

Patients with type 2 diabetes were older, more frequently male and had less often family history of premature CAD than non-diabetic patients. Non-diabetic patients had lower body mass index and were less often hypertensive, dyslipidemic or smoking as compared with patients having prediabetes or type 2 diabetes. There was no difference in the rate of angina pectoris among the 3 groups, but patients with type 2 diabetes had less frequently ischemia on exercise ECG. Patients with prediabetes or type 2 diabetes were more often using anti-ischemic medication, lipid-lowering medication, antithrombotic medication, and angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB), compared with non-diabetic patients.

Imaging findings

Obstructive CAD was excluded by coronary CTA alone in 1161 (67%) patients (normal coronary CTA in 597 patients and non-obstructive CAD in 564 patients). In turn, 582 (33%) patients underwent PET perfusion imaging for hemodynamic evaluation of suspected obstructive CAD, of whom 281 patients had normal and 301 had abnormal perfusion. The radiation dose was 7.5 ± 3.4 mSv from coronary CTA and 0.96 ± 0.18 mSv from PET perfusion imaging.

The prevalence of normal coronary arteries on CTA was highest in the non-diabetic patients (39%). In contrast, the prevalence of hemodynamically significant CAD (abnormal perfusion) increased from 14% in non-diabetic patients to 20% in prediabetic and 27% in diabetic patients (Table 1 and Fig. 2).

Fig. 2figure 2

Combined CTA/PET imaging findings according to diabetes status

Coronary artery calcium score was available for 1438 (83%) patients in the cohort, and the amount of coronary calcification was associated with the diabetes status (Table 1). The prevalence of zero calcium score was 41% in non-diabetic patients and decreased to 29% in prediabetic and 20% in diabetic patients. Conversely, the presence of high (> 400) calcium score was 12% in non-diabetic patients and increased to 17% in prediabetic and 33% in diabetic patients.

Annual rate of adverse events

During a median follow-up of 6.43 years (25th-75th percentiles 4.63–8.62), 164 adverse events were recorded, including 106 deaths, 41 MIs and 17 UAPs. In 597 patients with normal coronaries on CTA there were 8 adverse events (6 deaths and 2 MIs). In 564 patients with non-obstructive CAD there were 51 adverse events (39 deaths, 8 MIs and 4 UAPs). In 281 patients with suspected obstructive CAD but normal perfusion there were 36 adverse events (19 deaths, 15 MIs and 2 UAPs). In 301 patients with suspected obstructive CAD and abnormal perfusion there were 60 adverse events (33 deaths, 16 MIs and 11 UAPs).

Annual rate of composite endpoint (death/MI/UAP) was 1.33% (95% CI 1.14–1.56%) for the whole study cohort, 1.23% (95% CI 1.01–1.50%) in non-diabetic, 1.02% (95% CI 0.65–1.59%) in prediabetic patients, and 2.16% (95% CI 1.57–2.97%) in patients with type 2 diabetes. Patients with type 2 diabetes had higher event rate than non-diabetic patients (p = 0.003), whereas event rates were similar in prediabetic and non-diabetic patients (p = 0.450).

Figure 3 shows the annual event rate stratified by diabetes status and hybrid CTA/PET imaging findings. Figure 4 shows the annual event rate stratified by diabetes status and Agatston calcium score. The details of the event numbers and rates are shown in Additional file: Tables S1 and S2.

Fig. 3figure 3

Annual composite adverse event % rates (with 95% confidence intervals) stratified by diabetes status and combined CTA/PET imaging findings. Comprehensive statistics provided in Additional file 1: Table S1. *Indicates statistical significance

Fig. 4figure 4

Annual composite adverse event % rates (with 95% confidence intervals) stratified by diabetes status and Agatston calcium score. Comprehensive statistics provided in Additional file 1: Table S2

The rate of subsequent early ICA and early revascularization, respectively, after CTA/PET imaging were 0% and 0% in patients with normal coronary CTA, 2.8% and 0.2% with non-obstructive CAD, 6.0% and 1.1% with obstructive CAD but normal PET perfusion, and 57.1% and 37% with abnormal PET perfusion. Patients with type 2 diabetes underwent coronary revascularization more often than non-diabetic patients (11% vs. 6%, p = 0.002).

Predictors of adverse events

In Cox regression analysis, univariable predictors of adverse events were increasing age, male sex, type 2 diabetes, hypertension, typical angina pectoris, coronary artery calcium score and CTA/PET imaging findings (Table 2). In the multivariable model with hybrid CTA/PET imaging, age, hypertension, and hybrid imaging findings remained independent predictors of events, whereas neither prediabetes nor type 2 diabetes was independent predictor of events (Table 2). Likewise, in the multivariable model with coronary calcium score, age and coronary artery calcium score remained independent predictors of adverse events, whereas neither prediabetes nor type 2 diabetes was independent predictor.

Table 2 Cox proportional hazards model predictors for adverse events

Sub-analyses restricted to patients not undergoing early revascularization were carried out for both multivariable models: CTA/PET finding remained an independent predictor of outcome (p < 0.001) while type 2 diabetes did not (p = 0.597). Similarly, calcium score was an independent predictor (p < 0.001) while type 2 diabetes was not (p = 0.833).

There was no significant statistical interaction between diabetes status and CTA/PET imaging findings for predicting composite adverse endpoint (p-value 0.319). Similarly, there was no interaction between calcium score and diabetes status for predicting events (p-value 0.937).

Figure 5 shows Kaplan–Meier survival curves for CTA/PET imaging findings separately for patients with no diabetes, prediabetes, and type 2 diabetes. The most favourable outcome was associated with normal coronary CTA imaging finding, whereas the poorest outcome was associated with obstructive CAD and abnormal perfusion despite diabetes status. Survival between imaging finding groups was statistically different among patients with no diabetes (p-value < 0.001), prediabetes (p-value 0.004), and type 2 diabetes (p-value < 0.001).

Fig. 5figure 5

Kaplan-Meier survival curves of CTA/PET findings, stratified by diabetes status

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